Activin and inhibin are gonadal proteins that alter both pituitary and ovarian function. The work presented in the present proposal represents an extension of our previous studies of the effects of, and the role played by these proteins. We have observed that the peripheral administration of activin increased GnRH mRNA levels in the hypothalamus. Under Specific Aim 1, we will determine whether inhibin also alters GnRH gene expression; whether the effect of activin (and possibly inhibin) on GnRH transcripts are mediated by sex steroids; whether changes in brain GnRH levels are accompanied by altered release of the peptide from the median eminence; and whether endogenous opiates play a role in these effects. We will also investigate the role of activin during the estrous cycle and during the early increase in gonadotropin levels caused by gonadectomy, by blocking activin with specific neutralizing antibodies of the ligand binding domain. These experiments will address as yet unexplored aspects of the role and effects of inhibin/activin.